1. Field of the Invention
The present disclosure relates to a method for treating malignant pleural effusions (MPE) in a subject, particularly for treating MPE in a subject suffering from lung cancer, breast cancer, lymphoma, leukemia, or mesothelioma in a late stage by a novel pharmaceutical composition comprising benzenesulfonamides. The present disclosure also relates to a pharmaceutical composition comprising benzenesulfonamides and a process for preparation thereof.
2. Description of Related Art
Cancers with various origins have been serious diseases worldwide. The later stage of cancer is diagnosed, the lower cure rate is. Malignant pleural effusions (MPE) resulted from metastatic malignant pleural tumors or primary malignant pleural tumors is one of the most common complication of malignant tumors. It is reported that 24% to 50% of exudative pleural effusions originated from malignant lesions and 50% of tumor metastasis finally lead to MPE. Top three MPE generating cancers are lung cancer the first, breast cancer the second, and lymphoma the third. The primary cancer tumor lesions have not been found in about 5% to 10% of MPE cases. All malignant tumors excluding primary brain tumor and limbs tumor may generate MPE (Am J Respir Crit Care Med Vol. 162. P. 1987-2001, 2000).
MPE is often regarded as a complication in the late stage of tumors. MPE is rapidly developing and often complicated with the symptoms such as chest tightness, shortness of breath, palpitations, and unable supine. Delaying the treatment of MPE might cause barriers of respiration and circulation, hypoproteinemia, and anemia, and the severe symptoms might be life-threatening. Therefore, rapidly and effectively treating MPE is an important step in cancer therapy. However, the treatment of MPE is difficult due to high mortality rate. The one, three and six-month(s) mortality rates of patients with MPE are 50%, 60%, and 82%, respectively. The average life expectancy is merely 3.1 months. Effectively managing MPE has been one of the difficult issues in clinical treatments.
In clinical practice, removing pleural effusions and preventing its accumulation again, relieving symptoms, raising life quality, as well as extending survival period are the current main treatments for MPE. The major methods include chest drainage, video-assisted thoracic surgery (VATS), intrathoracic administration, pleural fixation, whole body chemotherapy, radiotherapy, thermal therapy and the like. However, limitation exists in each treatment application which results in limited therapy efficacy. Recently hyperthermic pleural perfusion treatment provides a new method and it is theoretically and technically supported. There are two kinds of hyperthermic pleural perfusion treatments: one is physiological saline, which exhibits low timeliness to pleural effusions control and high recurrence; the other is chemotherapy by cisplatin and so on, which is used for local anti-cancer and promoting pleural connection. However, over pleural connections are frequently observed in clinical practice, resulting in fibrin depositing on pleura, pleural capillaries and fibroblasts extending into fibrin and forming granulation tissue, gradually thickening to dense envelope and forming pleural fibreboard. The wide and rigid fibreboard wraps around the lung tissue and lacks flexibility, so as to limit chest expansion, severely reduce breath and increase the recurrence rate of pleural effusions. As a result, a pleural perfusion liquid effectively improving function of respiratory system and reducing recurrence rate remains a need yet to be met.
MPE is a secondary symptom of primary tumor. Therefore, the attention of clinical study and the improvement of treatment are relatively limited compared to other mainstream domains of tumor study. Meanwhile, the commercial profit is also limited. In view of the above problem of the conventional art, the technical purpose of the present disclosure is to provide a new medication with assured effect and fewer side effects to treat MPE. The study on MPE by benzenesulfonamides is so far underreported.
Chinese Patent Application No. 201010284152.0 discloses a Chinese medicine for treating MPE comprising the following Chinese herbs: Codonopsis pilosula 13-18 g, Astragalus membranaceus 28-32 g, prepared rhizome of Rehmannia glutinosa 13-18 g, Angelica sinensis 13-18 g, Fritillaria cirrhosa 8-12 g, Wolfiporia extensa 13-18 g, Semen lepidii 8-12 g, licorice 8-12 g, Chenpi 8-12 g, Trichosanthes kirilowii Maxim. 13-18 g, grifola 8-12 g, Rhizoma alismatis 8-12 g, the root of Paris polyphylla 8-12 g, Solanum lyratum 8-12 g.
Chinese Patent Application No. 201410315790.2 discloses a medical composition for treating MPE comprising the following Chinese herbs: Jacobinia suberecta 20-30 parts, herb of Villosulous veronicastrum 9-15 parts, Potentillae parvifoliae fisch 5-15 parts, Iris japonica 25-30 parts, Wusili dragonflyorchis rhizome 10-16 parts, Phaenosperma globosa 15-25 parts, Chorion ovi 3-8 parts, root of Dunn Antictrema 7-10 parts, Manyflower solomonseal rhizome 10-15 parts, Paris polyphylla 15-25 parts, Solanum lyratum 20-25 parts, Duchesnea indica 15-20 parts.
Chinese Patent Application No. 201510413494.0 discloses a medical composition for treating MPE comprising the following Chinese herbs: Panax quinquefolius 2-18 parts, Panax pseudo-ginseng 4-30 parts, Semen lepidii 2-18 parts, Pyrrosla lingua 3-21 parts, Zanthoxylum bungeanum Maxia. 2-8 parts, Cynanchi paniculati 10-50 parts, Trichosanthes kirilowii Maxim., 5-25 parts, fresh Astragalus 10-50 parts, Rhizoma alismatis 2-18 parts, Atracylodes macrocephalae 3-21 parts, Ziziphus jujuba Mill. 2-12 parts.
Chinese Patent Application No. 201510776648.2 discloses a medication for treating chi yin deficiency type MPE, comprising Codonopsis pilosula, Eleutherococcus senticosus, Scrophularia ningpoensis Hemsl., Plantago asiatica L., Semen lepidii, Ephedra, Ramulus Cinnamomi, Rheum Palmatum L., Morus alba, root of Dioscorea polystachya, Orchis italica, Curculigo orchioides, Levisticum officinale, root of Asparagus cochinchinensis, Japanese Honeysuckle, Ruta graveolens, Aster ageratoides Turcz., and Typha angustifolia L.
Chinese Patent Application No. 201510772076.0 discloses a medication for treating spleen phlegm type MPE, comprising Rheum palmatum L., Semen lepidii, roots of Curcuma wenyujin, Ramulus Cinnamomi, fruit of Large flower Gardenia, Iphigenia indica Kunth, Prunella vulgaris, Codonopsis pilosula, Zingiber oj-jicinale Rosc., Schisandra chinesis, cattle penis, oriental dodartia herb, Platycodon grandiflorus, Levisticum officinale, Ephedra, Liriope spicata, fruits of Arctium lappa L., Largehead atractylodes rhozome, Scrophularia ningpoensis Hemsl., Acorus tatarinowii Schott., and licorice.
There are certain methods in treating MPE by Chinese medicine based on five compound medications described above, but their clinical evidences of treating MPE are not sufficient yet. As such, the efficient results of the clinical treatment are hardly achieved due to the defect of five patented medications described above.